Sympathomimetic compounds, as the name implies, exert biological effects similar to those produced by activation of the sympathetic nervous system. For example, the pharmaceutical compound pseudoephedrine acts as an indirect sympathomimetic agent by causing adrenergic nerve endings to release norepinephrine, thereby stimulating alpha- and beta-norepinephrine receptors, particularly in blood vessels of the upper respiratory tract. This, in turn, results in vasoconstriction and shrinkage of swollen tissues in the sinuses and nasal passages, rendering such compounds useful as decongestants.
Despite their legitimate uses, acid salts of sympathomimetic amines (SA), such as the ubiquitous pseudoephedrine hydrochloride, pseudoephedrine sulfate, ephedrine hydrochloride and phenylpropanolamine hydrochloride, are often utilized in the synthesis of illegal drugs such as methamphetamine, amphetamine, methcathinone, and cathinone. One of the most efficient starting materials in the synthesis of methamphetamine is ephedrine, which is heavily regulated and therefore difficult to obtain. Increasingly, pseudoephedrine, a diastereomer of ephedrine, is being used in the production of methamphetamine. Pseudoephedrine can be obtained from a pseudoephedrine salt, such as pseudoephedrine hydrochloride, which is a common ingredient in over-the-counter (OTC) medications.
Pseudoephedrine hydrochloride may be isolated from OTC medications by first suspending/dissolving the commercial products in water. The resulting slurry/solution is filtered and then treated with base to neutralize the amine salt, thereby producing pseudoephedrine free base. The free base, which has limited water solubility, is then extracted into a water immiscible solvent such as ether. This extraction serves as a purification step. Acidification to regenerate the amine hydrochloride followed by extraction into water is normally adequate to produce suitably pure pseudoephedrine hydrochloride. Alternatively, one may use the free base without regenerating the salt form.
It has thus been found desirable to formulate sympathomimetic amine-containing products in order to render isolation of the sympathomimetic amine more difficult or otherwise interfere with efforts to produce illegal drugs from common OTC medications, e.g., by altering reactants used to convert sympathomimetic amine to methamphetamine.
For example, U.S. Pat. No. 6,136,864 to Nichols et al. discloses incorporation of one or more denaturant compounds, to render commercially available medications containing sympathomimetic amine salts much less suitable as starting materials in the production of illegal drugs. The denaturant(s) exhibit chemical or physical properties which make the isolation of the pure sympathomimetic amine salt difficult or essentially infeasible, resulting in compromised yields of illicit product. The denaturant can be a compound, e.g., quinine, whose separation from sympathomimetic amine salts is difficult or essentially infeasible, so that the synthesis of illegal drugs from the compositions of the invention is rendered impracticable and/or produces illegal drugs in an adulterated form. Alternately, the denaturant is a material that physically interferes with the extraction of the sympathomimetic amine salts from the pharmaceutical products (i.e., emulsifies and/or alters viscosity of the pharmaceutical products in solution), so that the purification of the sympathomimetic amine salts from the pharmaceutical products is rendered impractical. In one aspect, the denaturant reacts to provide a product of “unpleasant taste, smell, emetic effect, etc.,” e.g., sulfur-containing amino acids and nitrogen-containing denaturants.
U.S. Pat. No. 6,359,011 to Bess et al. and US 2002/0082304 to Bess et al. disclose a pharmaceutical composition comprising sympathomimetic amine salt and a combination inhibitor, e.g., amino polymer, which interferes with both the isolation of the amine as well as its conversion to another pharmacologically active compound, without altering amine release from the composition.
U.S. Pat. No. 6,197,314 to Einig discloses a pharmaceutical tablet whose active ingredient, e.g., pseudoephedrine, is blended with an extraction-preventing composition which contains i) surfactant, e.g., alkyl sulfonate and ii) a fat or gel former, e.g., hydroxypropylmethylcellulose. The tablet produces a creamy emulsion when extraction of the active is attempted.
US2004/0166063 to Siegel discloses a method for marking a pharmaceutical product, container or pharmaceutical packaging system with a scent to establish identity or source of a product.
U.S. Pat. No. 6,495,529 and US2003/0119915 to Booth, et al. disclose pharmaceutical compositions which include (−)-pseudoephedrine, substantially free of (+)-pseudoephedrine, and a carrier. (−)-Pseudoephedrine, like (+)-pseudoephedrine, acts as an effective decongestant, but without the latter's side effects and drug interactions. Moreover, (−)-pseudoephedrine's reduction yields (R)-methamphetamine, which has only one-tenth the psychoactivity of (S)-methamphetamine derived from (+)-pseudoephedrine, which discourages illicit drug manufacture from these pharmaceutical compositions.
US2005/0026298 to Bickett et al. provides a method for modifying liquid anhydrous ammonia to discourage theft by adding a dye, e.g., a xanthene dye, say, rhodamine, which stains any object in subsequent contact with the liquid anhydrous ammonia. The dye can be visible to the naked eye and so discourages the use of such liquid ammonia in illicit drug manufacture, inasmuch as the dye can stain illicit products, production areas and equipment, the manufacturers themselves and, ultimately, the drug user.
U.S. Pat. No. 6,852,891 to Murray et al. discloses a way to inhibit or prevent the use of anhydrous ammonia in a dissolving metal reduction process such as that used to convert pseudoephedrine, etc., to methamphetamine. The method adds to the anhydrous ammonia a chemical reagent capable of scavenging solvated electrons generated when metal is dissolved in the ammonia. Murray et al. use stoichiometric compounds capable of undergoing a finite number of one-electron reduction processes, e.g., urea, alpha-tocopherol (vitamin E) and derivatives thereof, pentamethylchromanol, trichloroethylene and 1,1,1,2-tetrafluoroethane. Alternately, catalytic compounds accelerating reaction of electrons with the amonia solvent to produce amide anion and hydrogen gase can be used, e.g., Fe(III) citrate, ferrocene, 2-chloro-6-(trichloromethyl)pyridine and 1,1,1,2-tetrafluoroethane. Murray et al. at col. 5, lines 63 to 67 teach that “[c]hoosing a compound which possesses a boiling point close to that of ammonia increases the likelihood that the compound will be carried over during a distillation of the ammonia, thus making removal of the compound from ammonia very difficult.” Use of this anhydrous ammonia substantially reduces methamphetamine yield.
All of the above references are incorporated herein by reference in their entirety.
Despite the various methods set out above which inhibit the isolation of sympathomimetic amines or otherwise inhibit illicit synthesis efforts, techniques have been developed which limit the effectiveness of these methods. For example, certain distillation techniques can be employed to separate denaturants from sympathomimetic amines.
Accordingly, it would be advantageous to provide additional methods for preventing or deterring illegal conversion of sympathomimetic amine compounds while maintaining OTC availability, particularly for overcoming distillation-based isolation of sympathomimetic amines.